Letrozole + Everolimus + TRC105 for Breast Cancer

Age: 18+
Sex: Female
Trial Phase: Phase 1 & 2
Sponsor: University of Alabama at Birmingham
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of three drugs—Letrozole, Everolimus, and TRC105—to evaluate their effectiveness in treating certain types of breast cancer before surgery. Letrozole and Everolimus block signals that promote cancer growth, while TRC105 aims to cut off the blood supply to the cancer. The goal is to determine if this drug combination is safe and effective for individuals with Stage 2 or 3 hormone receptor-positive, HER2-negative breast cancer. Those newly diagnosed with this type of breast cancer, who are postmenopausal and have not received prior treatment, may be suitable candidates for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of Letrozole, Everolimus, and TRC105 can cause some common side effects. Participants often experienced headaches, tiredness, facial redness, and swelling. Other reported issues included bleeding gums and nosebleeds. These side effects were common but varied in severity among individuals.

This trial is in its early stages, focusing mainly on safety and tolerability. These early phases are crucial for understanding the body's response to the combination. Letrozole and Everolimus are already approved for other uses, indicating a known safety profile. However, TRC105 remains under study, so its safety is less certain.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Letrozole, Everolimus, and TRC105 for breast cancer because it targets the disease in a unique way. Unlike standard treatments that often focus on hormone suppression or chemotherapy alone, this combination therapy adds an anti-angiogenic agent, TRC105, which works by inhibiting blood vessel growth that tumors need to thrive. Everolimus, an mTOR inhibitor, further disrupts cancer cell growth and survival pathways, while Letrozole continues to suppress estrogen production. This multi-faceted approach is promising because it simultaneously attacks cancer cells on multiple fronts, potentially leading to more effective outcomes and improved patient responses compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that combining everolimus with letrozole can prolong the period before cancer worsens. Everolimus has proven especially effective in certain types of breast cancer, particularly when the cancer has returned or spread. Letrozole blocks estrogen, a hormone that some breast cancers require for growth. TRC105, the investigational drug in this trial, inhibits blood vessels that support tumor growth. This trial will explore the combination of everolimus, letrozole, and TRC105, which findings suggest could be promising for treating breast cancer before surgery.15678

Who Is on the Research Team?

ES

Erica Stringer-Reasor, M.D.

Principal Investigator

University of Alabama at Birmingham

ES

Erica Stringer-Reasor, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with Stage 2 or 3 hormone receptor-positive and HER2-negative breast cancer, who haven't had treatment for it yet. They should be relatively healthy (ECOG < 2), have good blood counts and liver/renal function, and must consent to the study.

Inclusion Criteria

ANC ≥ 1,500/mm3, platelets ≥ 100,000/mm3, Hemoglobin ≥ 10g%.
Histological grade I, II or III according to the modified Bloom Richardson scale.
ECOG performance status < 2 (Karnofsky > 60%).
See 7 more

Exclusion Criteria

Metastatic disease.
Triple negative breast cancer (hormone receptor and Her2 negative).
Disease that cannot be followed by imaging studies.
See 4 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Determine the ideal combination of doses of Letrozole, Everolimus, and TRC105 for tolerance

4 weeks
Regular visits for dose-limiting toxicity assessment

Phase II Treatment

Participants receive the investigational combination of Letrozole, Everolimus, and TRC105 to assess preliminary efficacy

24 weeks
Bi-weekly visits for TRC105 administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Everolimus
  • Letrozole
  • TRC105
Trial Overview The trial tests a new drug combo: Letrozole (blocks estrogen receptors), Everolimus (stops cancer growth signals), and TRC105 (prevents blood vessel growth in tumors). It aims to see if this mix can safely improve outcomes before surgery.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Phase IIExperimental Treatment3 Interventions
Group II: Phase I Cohort 2Experimental Treatment3 Interventions
Group III: Phase I Cohort 1Experimental Treatment3 Interventions
Group IV: Phase I Cohort -1Experimental Treatment3 Interventions

Everolimus is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Afinitor for:
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Approved in European Union as Votubia for:
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Approved in United States as Zortress for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials
1,677
Recruited
2,458,000+

Tracon Pharmaceuticals Inc.

Industry Sponsor

Trials
22
Recruited
1,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials
2,963
Recruited
4,275,000+
Founded
1996
Headquarters
Basel, Switzerland
Known For
Precision medicine
Top Products
Gleevec, Cosentyx, Entresto, Kisqali
Dr. Vas Narasimhan profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

A phase I/II study of preoperative letrozole, everolimus, and ...The most frequent adverse events were headache (67%), fatigue (47%), facial flushing and swelling (47%), gingival hemorrhage (40%), epistaxis (33%), nausea and ...
Letrozole + Everolimus + TRC105 for Breast CancerResearch shows that combining everolimus with letrozole can improve progression-free survival (the time during which the cancer does not get worse) in patients ...
Combination of Letrozole, Everolimus and TRC105 in ...Everolimus has already been shown to work very well in this subtype of breast cancer in the recurrent and metastatic setting. TRC105 is an ...
Combination of Letrozole, Everolimus and TRC105 in ...Everolimus has already been shown to work very well in this subtype of breast cancer in the recurrent and metastatic setting. TRC105 is an investigational agent ...
UAB 1514 A Phase I/II Study of Preoperative (Neoadjuvant) ...Determine the efficacy of the combination of letrozole, everolimus, and TRC105 in postmenopausal women with newly diagnosed potentially resectable local or ...
Combination of Letrozole, Everolimus and TRC105 in ... - MedPathThis study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 ...
Trial | NCT02520063This study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 ...
Open-label, Phase II, Study of Everolimus Plus Letrozole in ...The purpose of this study was to assess the efficacy and safety of first-line treatment with everolimus plus letrozole in postmenopausal women with estrogen ...
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